Dynamic Imine Bonding Facilitates Mannan Release from a Nanofibrous Peptide Hydrogel.

Recently, there has been increased interest in using mannan as an immunomodulatory bioconjugate. Despite notable immunological and functional differences between the reduced (R-Man) and oxidized (O-Man) forms of mannan, little is known about the impact of mannan oxidation state on its in vivo persistence or its potential controlled release from biomaterials that may improve immunotherapeutic or prophylactic efficacy. Here, we investigate the impact of oxidation state on the in vitro and in vivo release of mannan from a biocompatible and immunostimulatory multidomain peptide hydrogel, K2(SL)6K2 (abbreviated as K2), that has been previously used for the controlled release of protein and small molecule payloads. We observed that O-Man released more slowly from K2 hydrogels in vitro than R-Man. In vivo, the clearance of O-Man from K2 hydrogels was slower than O-Man alone. We attributed the slower release rate to the formation of dynamic imine bonds between reactive aldehyde groups on O-Man and the lysine residues on K2. This imine interaction was also observed to improve K2 + O-Man hydrogel strength and shear recovery without significantly influencing secondary structure or peptide nanofiber formation. There were no observed differences in the in vivo release rates of O-Man loaded in K2, R-Man loaded in K2, and R-Man alone. These data suggest that, after subcutaneous injection, R-Man naturally persists longer in vivo than O-Man and minimally interacts with the peptide hydrogel. These results highlight a potentially critical, but previously unreported, difference in the in vivo behavior of O-Man and R-Man and demonstrate that K2 can be used to normalize the release of O-Man to that of R-Man. Further, since K2 itself is an adjuvant, a combination of O-Man and K2 could be used to enhance the immunostimulatory effects of O-Man for applications such as infectious disease vaccines and cancer immunotherapy.

Metacognition in the classroom: The association between students' exam predictions and their desired grades.

Students are overconfident when making grade predictions, and worse, the lowest-performing students are generally the most overconfident. Because metacognitive accuracy is associated with academic performance, multiple studies have attempted to improve metacognitive accuracy with mixed results. However, these studies may be of limited use because we do not understand the types of information university students use to make performance predictions. The current studies examined the possibility that university students' predictions are associated with their desires-the grade they want to receive. Studies 1-4 demonstrated that students' desired grades were strongly associated with their grade predictions across different courses, universities, and measurement strategies. Study 4 also showed that, if warned about the previous results, students could reduce their reliance on their desired grades and improve the accuracy of their predictions relative to control. Together, results demonstrated that students' exam predictions are associated with their desired grades.

An examination of younger and older adults' age preferences.

Research suggests that how people feel about aging can contribute to their later physical, cognitive, and mental health. In two studies, we examined younger (ages 18-30) and older adults' (ages 61-70) views about aging by asking them to rate the extent to which they would find it desirable to be various ages between 0 and 120. Participants also indicated both their ideal age (the age at which they would most like to be) and their subjective age (how old they generally feel). Consistent with the previous studies, younger adults' ideal age was significantly younger than older adults' ideal age. Younger adults' subjective age was slightly older than their chronological age, whereas older adults' subjective age was slightly younger than their chronological age. Of interest was the finding that, for older adults, their desirability ratings of various ages gradually decreased after age 35. In contrast, younger adults' desirability ratings decreased precipitously after age 20 and remained low from age 45 through age 90. Results suggest that older adults view middle to later life in a more nuanced manner than younger adults, who viewed middle and later life as being undesirable and homogenous. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Multidomain peptide hydrogel adjuvants elicit strong bias towards humoral immunity.

Adjuvants play a critical role in enhancing vaccine efficacy; however, there is a need to develop new immunomodulatory compounds to address emerging pathogens and to expand the use of immunotherapies. Multidomain peptides (MDPs) are materials composed of canonical amino acids that form injectable supramolecular hydrogels under physiological salt and pH conditions. MDP hydrogels are rapidly infiltrated by immune cells in vivo and have previously been shown to influence cytokine production. Therefore, we hypothesized that these immunostimulatory characteristics would allow MDPs to function as vaccine adjuvants. Herein, we demonstrate that loading antigen into MDP hydrogels does not interfere with their rheological properties and that positively charged MDPs can act as antigen depots, as demonstrated by their ability to release ovalbumin (OVA) over a period of 7-9 days in vivo. Mice vaccinated with MDP-adjuvanted antigen generated significantly higher IgG titers than mice treated with the unadjuvanted control, suggesting that these hydrogels potentiate humoral immunity. Interestingly, MDP hydrogels did not elicit a robust cellular immune response, as indicated by the lower production of IgG2c and smaller populations of tetramer-positive CD8+ T splenocytes compared to mice vaccinated alum-adjuvanted OVA. Together, the data suggest that MDP hydrogel adjuvants strongly bias the immune response towards humoral immunity while evoking a very limited cellular immune response. As a result, MDPs may have the potential to serve as adjuvants for applications that benefit exclusively from humoral immunity.

The effect of cognitive testing and feedback on older adults' subjective age.

Subjective age, or how old a person feels, is an important measure of self-perception that is associated with consequential cognitive and health outcomes. Recent research suggests that subjective age is affected by certain situations, including cognitive testing contexts. The current study examined whether cognitive testing and positive performance feedback affect subjective age and subsequent cognitive performance. Older adults took a series of neuropsychological and cognitive tests and subjective age was measured at various time points. Participants also either received positive or no feedback on an initial cognitive task, an analogies task. Results showed that participants felt older over the course of the testing session, particularly after taking a working memory test, relative to baseline. Positive feedback did not significantly mitigate this subjective aging effect. Results suggest that subjective age is malleable and that it can be affected by standard cognitive and neuropsychological test conditions.